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Biomedical subjects

P M Shah

Publications and source records attributed to P M Shah.

At least 19 recordsLinked to original sources

[Malaria tropica].

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Anti-Bacterial Agents

In vitro activity of cefodizime.

Cefodizime is a bactericidal cephem with the typical broad spectrum activity of an aminothiazolyl cephalosporin, including both gram-positive and gram-negative bacteria: its MIC90 is 0.125 mg/l for Streptococcus pneumoniae, Streptococcus pyogenes and other streptococci; and 0.05 mg/l for Haemophilus spp., Neisseria meningitidis, Neisseria gonorrhoeae and Moraxella catarrhalis; while beta-lactamase positive strains of M. catarrhalis require 1 mg/l. Less than 1 mg/l is needed for Escherichia coli, Klebsiella spp., Proteus spp. and Shigella spp. The MIC90 is 4 mg/l for methicillin-sensitive Staphylococcus aureus, Morganella morganii, Providencia spp. and most strains of Serratia marcescens, Citrobacter spp. and Enterobacter spp. Staphylococcus epidermidis, Enterococcus faecalis and most strains of Pseudomonas spp. and Acinetobacter spp. are considered cefodizime-resistant. Cefodizime is unaffected by plasmid-mediated beta-lactamases, but it is hydrolyzed by some chromosomally mediated enzymes, thus resembling other third-generation cephalosporins. Cefodizime has high affinity for PBP 3 and PBP IA and IB (Escherichia coli); in S. aureus it shows the highest affinity for PBP 1.

Bacteria

In vivo activity of cefodizime.

Cefodizime has been shown to possess high in vivo antibacterial activity in a variety of experimental infection models involving different body systems and animal species: systemic infections, pneumonia and urinary tract infections in normal mice, intrauterine infections in normal rats, and meningitis in normal rabbits, as well as systemic infections in immunosuppressed animals. Most investigations found that the therapeutic efficacy of cefodizime frequently exceeded the one expected from its in vitro values and in many cases compared favorably with those of other cephems, even when the in vitro susceptibility of the infecting organism to these drugs was markedly higher. These findings have been attributed either to the superior kinetic profile of cefodizime--prolonged serum half-life and excellent tissue penetration with long-lasting levels--or to a synergy between its high bactericidal activity and host defence mechanisms. The parallel consideration of the MIC90 values of cefodizime and the pharmacokinetic profile of this agent in humans indicate that the vast majority of the relevant respiratory and urinary pathogens are covered by once-a-day cefodizime dosage regimens of either 1 or 2 g.

Animals

Influence of cefodizime on the reagibility of human leukocytes.

Cefodizime was evaluated for its effect on a number of parameters of leukocyte function in humans. Four healthy volunteers received 2 g i.v. b.i.d. for seven days. Leukocyte activity was measured before, during and after treatment. Using opsonized zymosan as a stimulant, no effect on the respiratory burst of granulocytes was observed. It was found, however, that the lymphocytes in three of the four subjects showed significantly more marked proliferation rates in the mixed lymphocyte reaction after administration of cefodizime than at baseline. The stimulation indices subsequently returned to normal. This pilot study therefore demonstrated that cefodizime has biological response modifying properties in healthy humans.

Cefotaxime

Cefodizime host-defence enhancement: considerations of dose-response relationships in healthy volunteers.

Studies with cefodizime in animals have shown that this new aminothiazolyl cephalosporin, possessing a broad antibacterial spectrum, positively influences a number of immunological parameters. In most investigations in which different dosage regimens were compared, a bell-shaped dose-response relationship was determined, i.e. activity after higher doses returned to near-baseline levels. This finding is typical of most immunomodulating agents. On this basis, the results obtained in healthy subjects were reviewed. Studies for investigating the biological response modifying (BRM) properties of cefodizime have been conducted in this population with either 2 g once daily i.v. or--in the majority--with 2 x 2 g/day i.v. After seven days of treatment with 1 x 2 g daily, no relevant changes could be demonstrated in healthy subjects, whereas there was an increase in monocyte and granulocyte chemotaxis in a parallel group of patients with multiple myeloma. In contrast, treatment with 2 x 2 g daily induced higher lymphocyte responsiveness and significantly increased nonspecific phagocytosis of both neutrophils and monocytes. The experience in healthy volunteers clearly demonstrates that the latter dose, usually the highest required for antibiotic treatment with cefodizime, is still located on the upward slope of the dose-response curve of positive BRM effects.

Animals

Diastolic heart failure.

Diastolic heart failure is a distinct clinical entity increasingly seen in older patients and requires special awareness to make the diagnosis. Although no single laboratory test is identified for making a confident diagnosis of diastolic dysfunction as the pathogenetic mechanism for heart failure, a constellation of echocardiographic and radionuclear findings are helpful in most cases. Invasive assessment of LV diastole is laborious, requiring high-fidelity pressures and accurate measures of volumes, and these are rarely needed to diagnose the condition. It appears that prognosis is significantly better for those with normal systolic function, when compared with congestive heart failure caused by impaired systolic pump function. Finally, the therapeutic approaches are substantially different for the two groups. It must be emphasized that even patients with predominant myocardial systolic dysfunction have some combined diastolic dysfunction as well. This latter group is difficult to treat. However, improvement in systolic pump function, when markedly impaired, must take precedence in management strategies.

Diastole

Transesophageal echocardiography and the intraoperative management of pediatric congenital heart disease: initial experience with a pediatric esophageal 2D color flow echocardiographic probe.

Intraoperative color Doppler transesophageal echocardiography (TEE) was performed in 26 patients undergoing corrective or palliative surgery for congenital heart disease. Age ranged from 1 day to 15 years, and body weight ranged from 2.9 to 42 kg. Objectives of the study were to determine the smallest infant in whom the pediatric probe could be used safely, additional diagnostic value, and it role in the intraoperative assessment of the surgical repair. The insertion of the pediatric probe was possible in all 26 patients. The smallest infant in this series was a newborn weighing 2.9 kg. Excellent correlation was obtained with preoperative transthoracic echocardiographic findings and operative findings. Assessment of the surgical repair was obtained in the immediate postcardiopulmonary bypass period. No short-term complications occurred in this series. Intraoperative color Doppler TEE provided a detailed and accurate assessment of the morphology, the function of the heart, and altered the management of at least two patients.

Adolescent

In-vitro activity of cefpirome against isolates from patients with urinary tract, lower respiratory tract and wound infections.

The in-vitro activity of cefpirome, a new injectable cephalosporin, was compared with that of several other antibiotics against bacterial isolates from hospitalized patients with lower respiratory tract infections, urinary tract infections and wound infections. Minimum inhibitory concentrations were determined for 874 strains against 16 antibiotics using a microtitration technique. Cefpirome showed a very broad spectrum of activity against most pathogens tested. The spectrum included organisms such as Staphylococcus spp., enterococci, Enterobacter spp., and Pseudomonas spp. which are frequently resistant to third generation cephalosporins.

Anti-Bacterial Agents

Comparison of clinical response to cefpirome treatment and minimum inhibitory concentration of causative isolates. Microbiological and Clinical Study Groups.

Three hundred and forty-five clinical isolates from patients treated with cefpirome were studied using an MIC methodology to develop tentative breakpoints for cefpirome, and to correlate clinical success with in-vitro susceptibility. No relationship between elimination, persistence and MIC of potential pathogens was found. There was, however, a close relationship between clinical cure and improvement and eradication of causative organisms. Based on the data, tentative breakpoints of less than 4 mg/L for sensitive and greater than 16 mg/L for resistance, at a cefpirome dose of 2.0 g bid or 1.0 g bid for urinary tract infection, are suggested.

Bacteria

Influence of cefpirome on pharyngeal and faecal flora after single and multiple intravenous administrations of cefpirome to healthy volunteers.

The effect of single and multiple 2 g doses of i.v. cefpirome on pharyngeal and faecal flora was studied in ten male volunteers. There was no effect on pharyngeal flora. After a single dose, cefpirome had no effect on faecal flora but numbers of Escherichia coli were reduced below the detection limit during multiple dose treatment. No strains of Clostridium difficile were selected in this study and only a slight increase in the numbers of Candida spp. were found. Cefpirome, therefore, has little, if any, effect on faecal or pharyngeal flora.

Adult

Evaluation of biplane color Doppler transesophageal echocardiography in 200 consecutive patients.

BACKGROUND: We developed the first biplane transesophageal echocardiography (TEE) probe with two orthogonal transducers, allowing synchronous side-by-side displays of the heart on a monitor TV, and compared its diagnostic value with that of conventional single-plane TEE using commercially available Doppler equipment in 200 consecutive patients intraoperatively, perioperatively, or on an outpatient basis. METHODS AND RESULTS: Insertion was easy, except in one patient with a mediastinal tumor, and no complications were encountered. Both transverse and longitudinal scans allowed correct identification of true and false lumina in all 30 aortic dissection examinations, but longitudinal scanning was slightly superior in detecting types I and III entry sites. Three entries that were not detected by transverse scanning (two of DeBakey type I and one of type III) were visualized by longitudinal scanning. Among 37 cases of mitral regurgitation (MR), longitudinal scans were significantly superior (p less than 0.05) in revealing multiple jets (nine compared with two with transverse scanning). Although both planes yielded almost identical mean values for the maximum jet areas, a difference of over 50% in jet area size on the two planes was observed in 19 cases. The measured jet areas showed significant correlation with the angiographic MR grading, especially for the larger of the biplane measurements (p less than 0.01), and different grades showed little overlap. Longitudinal images increased the acoustic window of the heart and aorta from the esophagus. Moreover, longitudinal scanning provided good visualization of both ventricular outflow tracts, the ascending aorta, main pulmonary artery, and superior vena cava. CONCLUSIONS: This modality greatly facilitates a three-dimensional comprehension of cardiovascular lesions and flow dynamics, especially in aortic dissection and MR, and its safety was demonstrated. Our data demonstrate the usefulness of this new technique in comparison with conventional single-plane TEE.

Aortic Dissection

Effect of amphotericin B alone or in combination with rifampicin on phagocytosis of Candida species by human polymorphonuclear leukocytes.

The influence of amphotericin B and rifampicin alone and in combination on the killing of Candida albicans, Candida tropicalis and Cryptococcus neoformans by human polymorphonuclear leukocytes was investigated in vitro. Granulocytes were harvested from the blood of healthy volunteers and resuspended with the above mentioned fungi. After 6 hours, 81.5% of C. albicans, 97% of C. tropicalis but only 34% of C. neoformans were killed. The activity of amphotericin B against C. albicans and C. tropicalis was better in granulocyte-free medium. A synergism between amphotericin B and rifampicin towards Candida could be detected. It was also demonstrated in the presence of polymorphonuclear leukocytes with a factor > 1 log in reduction of colony count. However, whether granulocytes were present or not, rifampicin (4 mcg/mL) alone did not exert any influence on growth of Candida.

Adult

A simple noninvasive measurement of stenotic mitral valve area: an alternative approach using M-mode and Doppler echocardiography.

Doppler echocardiography is a widely used noninvasive technique to examine the mitral valve area (MVA) by obtaining mitral pressure half-time (PHT) and to assess the severity of the stenosis. However, several hemodynamic factors influence the PHT and may render the PHT data inaccurate in any measurement of MVA under certain conditions. Using a simple echo-Doppler (E-D) method, we assessed the MVA in a physiological equation. The mitral flow volume (MFV) is represented by MVA x transmitral mean flow velocity (mV) x diastolic filling time (DFT). Thus, the formula can be restated as MVA (cm2) = MFV (cm3)/mV (cm/sec) x DFT (sec). We measured MFV by M-mode, and mV and DFT by continuous wave Doppler echocardiography. This formula was tested in 43 patients with isolated mitral stenosis. MVA was obtained by the PHT and E-D methods, and the data obtained were validated against the results of cardiac catheterization. The results obtained using the E-D method showed much better correlation (r = 0.82) with those of catheterization than those with the PHT method (r = 0.52). The inter- and intraobserver variabilities were checked. The results obtained with the E-D method were found to be reproducible. To further validate the accuracy of the E-D method, MVA was measured by both methods at different R-R intervals after exercise and the results were compared. The MVA obtained by the PHT method showed marked variations; whereas, that obtained by the E-D method remained nearly constant. Similarly, in a patient with atrial fibrillation, the MVA assessed by the PHT method varied from beat to beat; whereas, the fluctuations in MVA were minimal using the E-D method. We concluded that the E-D method can be reliable and clinically easily applicable for the accurate assessment of MVA.

Adult

[Enhanced lymphocyte proliferation in the presence of epidermal cells of HIV-infected patients in vitro].

Clinical observations show that the HIV infection is often associated with affections of the skin. In order to examine the involvement of the epidermal immune system in the HIV infection, we determined accessory cell function of epidermal cells from HIV-1-infected patients. For this we measured the proliferative response of enriched CD(4+)-T-lymphocytes from HIV-infected patients and noninfected controls to stimulation with anti-CD3 and IL-2 in the presence of epidermal cells; the enhancement of the response is dependent on the presence of functionally intact accessory cells. The capacity of epidermal cells to increase the anti-CD3-stimulated T-cell proliferative response was significantly enhanced in HIV patients (CDC III/IVA) as compared with noninfected donors. It is discussed, whether the increased activity of epidermal cells from HIV-infected patients may be responsible for several of the dermal lesions in the course of an HIV infection as due to an enhanced production and release of epidermal cell-derived cytokines.

Adult

Meticulously restored lumina of injured veins remain patent.

We report our experience with 38 major venous injury repairs in 37 patients between January 1981 and December 1989. The injuries were caused by gunshot (n = 27), shotgun (n = 3), knife (n = 5), blunt trauma (n = 1), and dog bite (n = 1). These involved 27 femoral, 10 popliteal, and one brachial veins. Thirty patients had associated major arterial injuries and seven had major long bone fractures. Retrospective analysis yielded two groups. Group I consisted of 17 patients who underwent meticulous restoration of venous lumina ensured by intraoperative postreconstruction venography (IPV) in all patients. Two of these required revision on the basis of IPV findings. Late patency of venous repair was confirmed by postoperative venography (n = 10) or duplex scans (n = 7). All 17 venous repairs were patent (100%). In group II none of the 20 patients (21 veins) underwent IPV. Fifteen of the 20 patients underwent venography and five patients (six veins) underwent duplex scanning after surgery. Eight veins were occluded and 13 (62%) were patent. The difference in patency rates of venous repair between groups I and II was significant (p = 0.02). Three (37.5%) of eight patients with occluded venous repair required delayed fasciotomy, but only 1 (3.4%) of 29 limbs (30 veins) with patent lumina required fasciotomy (p = 0.03). We conclude that meticulous restoration to normal-caliber venous lumina, confirmed by IPV, can achieve high patency and low morbidity rates.

Adolescent